Sustained release small molecule drug formulation

Abstract

An injectable depot formulation includes a biocompatible polymer, an organic solvent combined with the biocompatible polymer to form a viscous gel, and a small molecule drug incorporated in the viscous gel such that the formulation exhibits an in vivo release profile having a C max to C min ratio of less than 200 and a lag time less than 0.2.

What is claimed is: 
     
       1. An injectable pharmaceutical composition comprising from about 10 wt % to about 30 wt % of risperidone base suspended in a gel comprising: (i) from about 40 wt % to about 60 wt % of a copolymer of lactic acid and glycolic acid, wherein the lactic acid to glycolic acid monomer ratio is from about 100:0 to about 60:40, and wherein the copolymer has a number average molecular weight from about 5,000 Daltons to about 30,000 Daltons, and (ii) benzyl benzoate, benzyl alcohol, ethyl benzoate, triacetin, N-methyl-2-pyrrolidone, or a combination of two or more thereof. 
     
     
       2. The composition of  claim 1 , wherein the gel consists of (i) and (ii). 
     
     
       3. An injectable pharmaceutical composition comprising from about 1 wt % to about 50 wt % of risperidone base suspended in a gel comprising: (i) from about 5 wt % to about 80 wt % of a copolymer of lactic acid and glycolic acid, and (ii) benzyl benzoate, benzyl alcohol, ethyl benzoate, triacetin, N-methyl-2-pyrrolidone, or a combination of two or more thereof. 
     
     
       4. The composition of  claim 3 , comprising from about 5 wt % to about 40 wt % of risperidone base. 
     
     
       5. The composition of  claim 4 , comprising from about 5 wt % to about 30 wt % of risperidone base. 
     
     
       6. The composition of  claim 5 , comprising from about 10 wt % to about 30 wt % of risperidone base. 
     
     
       7. The composition of  claim 3 , wherein the gel comprises: (i) from about 20 wt % to about 70 wt % of a copolymer of lactic acid and glycolic acid, and (ii) benzyl benzoate, benzyl alcohol, ethyl benzoate, triacetin, N-methyl-2-pyrrolidone, or a combination of two or more thereof. 
     
     
       8. The composition of  claim 7 , wherein the gel comprises: (i) from about 40 wt % to about 60 wt % of a copolymer of lactic acid and glycolic acid, and (ii) benzyl benzoate, benzyl alcohol, ethyl benzoate, triacetin, N-methyl-2-pyrrolidone, or a combination of two or more thereof. 
     
     
       9. The composition of  claim 3 , wherein the lactic acid to glycolic acid monomer ratio in the copolymer is from about 100:0 to 60:40. 
     
     
       10. The composition of  claim 9 , wherein the lactic acid to glycolic acid monomer ratio in the copolymer is from about 100:0 to 75:25. 
     
     
       11. The composition of  claim 3 , wherein the copolymer has a number average molecular weight from about 1,000 Daltons to about 120,000 Daltons. 
     
     
       12. The composition of  claim 11 , wherein the copolymer has a number average molecular weight from about 5,000 Daltons to about 30,000 Daltons. 
     
     
       13. The composition of  claim 3 , wherein the gel consists of (i) and (ii). 
     
     
       14. An injectable pharmaceutical composition comprising risperidone base suspended in a gel comprising: (i) a copolymer of lactic acid and glycolic acid, and (ii) benzyl benzoate, benzyl alcohol, ethyl benzoate, triacetin, N-methyl-2-pyrrolidone, or a combination of two or more thereof. 
     
     
       15. A method of administering risperidone base to a subject in need thereof, the method comprising subcutaneously injecting the composition of  claim 1  into the subject once per month. 
     
     
       16. A method of administering risperidone base to a subject in need thereof, the method comprising subcutaneously injecting the composition of  claim 3  into the subject once per month. 
     
     
       17. A method of administering risperidone base to a subject in need thereof, the method comprising subcutaneously injecting the composition of  claim 14  into the subject once per month. 
     
     
       18. A syringe comprising the composition of  claim 1 . 
     
     
       19. A syringe comprising the composition of  claim 3 . 
     
     
       20. A syringe comprising the composition of  claim 14 .